Our group has previously shown that bombesin/gastrin releasing peptide (BN/GRP) functions as an "autocrine growth factor" for human small cell lung cancer (SCLC). We have produced a monoclonal antibody (2A11) to this peptide which inhibits the clonal growth of SCLC in vitro and in vivo in nude mouse xenografts. In addition, we have shown that rabbit anti-idiotypic antiserum to 2A11 blocks bombesin/SCLC receptor interaction and stimulates the clonal growth of SCLS in vitro. The rabbit antiserum represents a heterologous mixture of many different types of anti-idiotypic antibodies some having agonistic and some showing antagonistic properties. In an effort to dissect such function we have generated syngenic monoclonal anti-idiotypic antibodies against 2A11 with the hopes of finding an antagonistic reagent capable of blocking "autocrine growth" at the receptor level. The cDNA gene for BN/GRP has recently been cloned by Eliot Spindel and Joel Habner at Massachusetts General Hospital in Boston. The BN/GRP mRNA encodes a precursor of 148 amino acids containing a typical signal sequence, human BN/GRP and the mid portion and carboxy-terminal region of the extension peptide. Rabbit polyclonal antiserum has been generated against these peptides and is now being used as an immunohistochemical reagent to assess the expression of gene products in SCLC cell lines.